This project addresses emerging problems with Dengue (DEN) in Mexico. DEN and dengue hemorrhagic fever (DHF) have emerged as major public health problems. Indeed, more than 2 billion people are at risk for DEN infection, millions are infected annually with an estimated 100,000 cases of life threatening DHF, and the situation continues to deteriorate. Unfortunately, the epidemiologic circumstances that led to the emergence of DHF as a major public health problem in Southeast Asia in the 1960s and 1970s are now occuring in tropical America and Mexico. The vector mosquito, Aedes aegypti, is hyperendemic, and another major vector, Aedes albopictus, is invading the country and may exacerbate the situation. Multiple serotypes and strains of DEN are now circulating simultaneously, and ominously, the incidence of DHF is increasing rapidly and DEN epidemics are occuring in cities in Northern Mexico. In this grant, we will, with colleagues from the Instituto Politecnica Nacional in Mexico City, from the Universidad Autonoma of Nuevo Leon in Monterrey, and the Universidad Autonoma of the Yucatan in Merida, investigate and elucidate the vector and viral genetic determinants of DEN transmission and virulence. This information will be used to develop and characterize biomarkers of vectors and viruses that pose substantial risk to human populations. Such information could be used to focus limited resources and and talents for control on situations with epidemic potential. Definition of vector and virus genotypes associated with DEN/DHF will permit eventual elucidation of mechanisms that determine virus transmission, disease, and epidemic potential and may lead to novel control and surveillance strategies for DEN in North America and elsewhere. These proposed studies will also provide invaluable information concerning the application of developed new technologies and approaches to other vector borne diseases of current and future public health importance.